Objective: To characterize longitudinal trajectories of testicular development in boys and breast development in girls, so as to provide reference data for understanding patterns of pubertal sexual maturation. Methods: Based on the Shanghai Pudong New Area Cohort Study on Growth, Development and Health in Children and Adolescents, a baseline survey was conducted in 2020 using a mult stage cluster random sampling method. A total of 2 184 children who completed all follow ups during the primary school period from 13 elementary schools in Pudong New Area,Shanghai,with annual follow ups during 2021-2025. Testicular volume and Tanner stage of breast development were assessed by professional physicians using standardized visual inspection and palpation. The age distribution of testicular volume and breast development was fitted by using cumulative link mixed models and Turnbull s nonparametric maximum likelihood estimation method. Results: Median ages for testicular volumes of 2, 3, 4 and 5 mL in boys were 7.07, 9.24, 10.29, and 11.57 years old, respectively. Median ages for Tanner breast stages Ⅱ, Ⅲ, Ⅳ, and Ⅴ in girls were 8.55 , 10.17, 11.18, and 13.78 years old, respectively. Based on overweight and obesity, stratified analysis showed that earlier pubertal onset among overweight/obesity children, and the key milestones for pubertal initiation were testicular volume reaching 4 mL in boys and breast Tanner II in girls for 10.29, 10.83; 8.18, 9.00 years. Conclusion Overweight and obesity are associated with earlier pubertal initiation,but there are certain gender and developmental stage specific patterns.

Background: High-mobility group box protein 1 (HMGB1) is a chromatin-binding protein involved in arthritis, ischemia, sepsis, atherosclerosis, neurodegenerative disorders, meningitis, and cancer. HMGB1 exhibits dual roles in cancer, acting as either a tumor suppressor or oncoprotein depending on context. Objective: This research aimed to elucidate HMGB1’s functional significance in cutaneous squamous cell carcinoma (cSCC). Methods: We overexpressed HMGB1 in cSCC cell lines using recombinant adenovirus and examined its effects on cell proliferation, colony formation, and cell migration. Results: Immunohistochemical analysis revealed elevated HMGB1 expression levels in cSCC tissue relative to normal epidermis. To assess the influence of HMGB1, we employed recombinant adenoviruses expressing HMGB1 to transduce SCC cell lines (SCC12 and SCC13). Enhanced HMGB1 expression significantly promoted cellular proliferation and colony formation capacity.Notably, HMGB1 overexpression elevated the levels of proliferation regulators, including P63, SOX2, CDK4 and CDK6. Furthermore, HMGB1 overexpression substantially enhanced tumor invasiveness, accompanied by upregulation of epithelial-mesenchymal transition (EMT) biomarkers. Mechanistically, overexpression of HMGB1 enhanced transforming growth factor-β signaling by increasing phosphorylation of SMAD2/3, the key mediators of EMT. Conclusion These data imply that HMGB1 acts as a tumor-promoting factor in cSCC.

ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis （CAG） through the phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group （n=14） and modeling group （n=44）. Rats in the blank group were fed routinely， while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine （MNNG） at a concentration of 140 μg/ml， combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling， the rats were randomly divided into model group （n=10）， inhibitor group （n=10） and moxibustion group （n=20）. After 40 minutes of suspended moxibustion at "Zhongwan" （CV 12） daily， the rats in the moxibustion group were divided into heat-sensitive moxibustion group （n=10） and non-heat-sensitive moxibustion group （n=9） according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily， and then administered with PI3K/Akt signaling pathway inhibitor， rapamycin solution， by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days， while the blank group received no intervention. After the intervention finished， the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 （MMP7）， vascular endothelial growth factor A （VEGFA） and epidermal growth factor receptor （EGFR） in gastric mucosa. The mRNA expression levels of PI3K， Akt and mammalian target of rapamycin （mTOR） in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt （p-Akt） and phosphorylated mTOR （p-mTOR） in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group， rats in all other groups exhibited decreased body weight， significantly increased gastric mucosal cell apoptosis-positive rates， elevated protein levels of MMP7， VEGFA and EGFR in gastric mucosa， increased mRNA expression levels of PI3K， Akt and mTOR， and enhanced protein expression levels of p-Akt and p-mTOR （P＜0.05 or P＜0.01）. Histopathological examination revealed thinning of the gastric mucosa， glandular disorganization and atrophy， accompanied by intestinal metaplasia.Compared to the model group， the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators （P＜0.05 or P＜0.01）. Compared to the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis； the non-heat-sensitive moxibustion group showed increased protein levels of MMP7， VEGFA and EGFR， as well as mRNA expression levels of PI3K， Akt and mTOR， and protein expressions of p-Akt and p-mTOR； the inhibitor group exhibited elevated protein expression level of EGFR （P＜0.05 or P＜0.01）. Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly， with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway， thereby reducing gastric mucosal cell apoptosis.

ObjectiveTo investigate the potential mechanism of heat-sensitive moxibustion on chronic atrophic gastritis （CAG） through the phosphoinositide 3-kinase/protein kinase B （PI3K/Akt） signaling pathway. MethodsFifty-eight SD rats were randomly divided into blank group （n=14） and modeling group （n=44）. Rats in the blank group were fed routinely， while the rats in the modeling group received drinking water containing 1-methyl-3-nitro-1-nitrosoguanidine （MNNG） at a concentration of 140 μg/ml， combined with irregular fasting and feeding for 12 weeks to establish CAG model. After successful modeling， the rats were randomly divided into model group （n=10）， inhibitor group （n=10） and moxibustion group （n=20）. After 40 minutes of suspended moxibustion at "Zhongwan" （CV 12） daily， the rats in the moxibustion group were divided into heat-sensitive moxibustion group （n=10） and non-heat-sensitive moxibustion group （n=9） according to the change of tail temperature during moxibustion. The inhibitor group was bound for 40 minutes daily， and then administered with PI3K/Akt signaling pathway inhibitor， rapamycin solution， by gavage at a dose of 1 mg/kg. The model group received intragastric administration of 1 ml/kg normal saline after 40 minutes of restraint stress each day. All interventions were administered once daily for 28 consecutive days， while the blank group received no intervention. After the intervention finished， the body weight of rats in each group was compared. HE staining was used to observe the histopathological changes of gastric mucosa. The apoptosis-positive rate of gastric mucosal cells was detected by TUNEL assay. Immunohistochemistry was performed to determine the protein levels of matric metalloproteinase-7 （MMP7）， vascular endothelial growth factor A （VEGFA） and epidermal growth factor receptor （EGFR） in gastric mucosa. The mRNA expression levels of PI3K， Akt and mammalian target of rapamycin （mTOR） in gastric mucosal tissues were detected by qPCR. The protein levels of phosphorylated Akt （p-Akt） and phosphorylated mTOR （p-mTOR） in rat gastric mucosal tissues were measured by Western Blotting. ResultsCompared to the blank group， rats in all other groups exhibited decreased body weight， significantly increased gastric mucosal cell apoptosis-positive rates， elevated protein levels of MMP7， VEGFA and EGFR in gastric mucosa， increased mRNA expression levels of PI3K， Akt and mTOR， and enhanced protein expression levels of p-Akt and p-mTOR （P＜0.05 or P＜0.01）. Histopathological examination revealed thinning of the gastric mucosa， glandular disorganization and atrophy， accompanied by intestinal metaplasia.Compared to the model group， the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group all showed significant improvements in the above-mentioned indicators （P＜0.05 or P＜0.01）. Compared to the heat-sensitive moxibustion group， the non-heat-sensitive moxibustion group and the inhibitor group exhibited increased positive rates of gastric mucosal cell apoptosis； the non-heat-sensitive moxibustion group showed increased protein levels of MMP7， VEGFA and EGFR， as well as mRNA expression levels of PI3K， Akt and mTOR， and protein expressions of p-Akt and p-mTOR； the inhibitor group exhibited elevated protein expression level of EGFR （P＜0.05 or P＜0.01）. Histopathological examination showed that the gastric mucosal glands in the heat-sensitive moxibustion group were arranged more regularly， with an approximately normal structural appearance. ConclusionHeat-sensitive moxibustion can improve the body weight of CAG rats and repair gastric mucosal injury. Its therapeutic effects may be mediated by inhibiting excessive activation of gastric mucosal PI3K/Akt signaling pathway， thereby reducing gastric mucosal cell apoptosis.

Objective:To investigate the protective effect of Dendrobium officinale polysaccharides(DOP)on intestinal mucosal barrier damage,and to elucidate the possible mechanism.Methods:Ten female C57BL/6 mice,aged 5 months,were selected as young group;twenty femal C57BL/6 mice,aged 15 months,were randomly divided into aged group and DOP treatment group(200 mg·kg-1,DOP group),with 10 mice in each group.The mice in DOP group were administrated with DOP by gavage.The body mass,food intakes and hanging time of the mice in various groups were detected.HE staining was used to observe the pathomorphology of intestinal and spleen tissues of the mice in various groups.Immunohistochemical staining was used to detect the expressions of intestinal atresin 1(ZO-1)and Mucin 2(MUC2)in intestinal tissue of the mice in various groups.The intestinal baterial metabolite medium(IBMM)were prepared to intervene the Caenorhabditis elegans(C.elegans),and the C.elegans were randomly divided into Young-IBMM group,Aged-IBMM group,and DOP-IBMM group.Immuno-fluorescence method was used to analyze the intestinal lipofuscin accumulation levels on the 1st day and the 12th day of the C.elegans in various groups.Brilliant blue staining was used to assess the intestinal leakage on the 1st day and the 12th day of C.elegans in various groups.The Caco-2 cells were randomly divided into Young-IBMM,Aged-IBMM and DOP-IBMM groups,and Western blotting method was used to detect the expression levels of ZO-1,Occludin,tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),phosphorylated myosin light chain(p-MLC),myosin light chain kinase(MLCK)proteins in the Caco-2 cells in various groups.Results:Compared with young group,the body mass of the mice in aged group was increased(P＜0.05),the amount of food intake was decreased(P＜0.05),and the hanging time was decreased(P＜0.05);compared with aged group,the body mass of the mice in DOP group was significantly decreased(P＜0.01),the amount of food intake was increased(P＜0.05),and the hanging time was significantly extended(P＜0.01).The HE staining results showed that compared with young group,the thickness of intestinal mucosa of the mice in aged group became thinner,the goblet cells were reduced,the intestinal villi were disordered with different lengths,a large amount of hemosiderin was found on the surface of the spleen,the cell components in the red medullary were reduced,and the lymphatic sheath and lymphatic nodes around the intra-white pulp artery remained or almost disappeared;compared with aged group,the thickness of the intestinal mucosa of the mice in DOP group was increased,the goblet cells were increased,the length of the intestinal villi was consistent and neatly arranged,the overall function of the red pulp of the spleen was improved,and the components of the white pulp were increased.The immunohistochemical staining results showed that compared with young group,the expression levels of ZO-1 and MUC2 proteins in intestinal tissue of the mice in aged group were significantly decreased(P＜0.05 or P＜0.001);compared with aged group,the expression levels of ZO-1 and MUC2 proteins in the intestinal tissue of the mice in DOP group were significantly increased(P＜0.05 or P＜0.001).The immuno-fluorescence analysis showed that compared with Young-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in Aged-IBMM group was significantly increased(P＜0.001);compared with Aged-IBMM group,the intestinal lipofuscin accumulation level of C.elegans in DOP-IBMM group was significantly reduced(P＜0.001).The brilliant blue staining showed that compared with Young-IBMM group,the bright blue dye leaked into the whole body of C.elegans from intestinal tissue in Aged-IBMM group,and the intestinal structure became blurred and was difficulted to be observed;compared with Aged-IBMM group,the leakage of bright blue dye of C.elegans in DOP-IBMM was reduced.The Western blotting results showed that compared with Young-IBMM group,the expression levels of TNF-α,IL-6,p-MLC,and MLCK proteins in the Caco-2 cells in Aged-IBMM group were significantly increased(P＜0.01 or P＜0.001),and the expression levels of ZO-1 and Occludin proteins were significantly decreased(P＜0.05 or P＜0.01);compared with Aged-IBMM,the expression levels of TNF-α,IL-6,p-MLC and MLCK proteins in the Caco-2 cells in DOP-IBMM group were significantly decreased(P＜0.01),and the expression levels of ZO-1 and Occludin proteins were significantly increased(P＜0.05 or P＜0.01).Conclusion:DOP has an ameliorating effect on intestinal mucosal barrier damage in the aged mice,and its mechanism may be related to the improvement of intestinal barrier damage by regulating intestinal bacterial metabolites,inhibiting the p-MLC/MLCK signal pathway,restoring the expression of tight junction complexes,and reducing the level of intestinal inflammation.

With the rapid development of competitive sports, the incidence of anterior cruciate ligament (ACL) injury is on the rise. Such injuries may shorten athletes′ career and lead to other long-term adverse consequences. Although athletes generally recover well after ACL reconstruction, many still struggle to return to their pre-injury performance levels. Advances in the understanding of ACL anatomy and injury mechanisms, along with the evolution of surgical techniques and rehabilitation methods, have provided more individualized and tailored options for athletes following ACL injuries. However, there is currently no consensus in China regarding surgical and rehabilitation strategies for competitive athletes aiming to return to sports after ACL injuries. To this end, the Sports Medicine Committee of the Chinese Research Hospital Association and the Editorial Board of the Chinese Journal of Trauma jointly formulated the Expert consensus on surgical treatment and rehabilitation for competitive sports athletes returning to sports after anterior cruciate ligament injury ( version 2025), and presented 14 recommendations covering surgical indications, preoperative rehabilitation, surgical timing, surgical strategies and postoperative rehabilitation strategies, aiming to improve the surgical treatment and rehabilitation system for ACL injuries in competitive athletes and facilitate their return to high-level sports performance after injury.

Postoperative infection of internal fixation of closed fractures the lower limbs in adults represents a devastating complication, characterized by diagnostic challenges, prolonged treatment duration and high disability rates. Current management of these infections faces multiple challenges, such as difficulties in early accurate diagnosis, and various controversies about the treatment plan, leading to poor overall diagnosis and treatment results. To address these issues, based on evidence-based medicine and principles with emphasis on scientific rigor, clinical applicability and innovation, the Trauma Branch of the Chinese Medical Association, Orthopedic Branch of the Chinese Medical Doctor Association, Orthopedics Branch of the Chinese Medical Association, and Trauma Orthopedics and Polytrauma Group of the Resuscitation and Emergency Committee of the Chinese Medical Doctor Association have collaboratively organized a panel of relevant experts to develop the Guideline for diagnosis and treatment of infection after internal fixation of closed lower limb fractures in adults ( version 2025). The guideline proposed 10 recommendations, aiming to provide a foundation for standardized diagnosis and treatment of postoperative infection in adults with closed lower limb fractures.

Acute lateral ankle sprain (ALAS) is one of the most common sport injuries, with high incidence, recurrence and disability rates. Currently, exercise rehabilitation-based non-surgical treatment is the primary management approach for ALAS. However, there remain improper practices such as excessive immobilization or uncontrolled activity, which contribute to recurrent sprains and chronic ankle instability, significantly impairing patients′ athletic function and quality of life. To standardize the non-surgical management of ALAS, improve the cure rates, and reduce the recurrence and disability rates, Chinese Sports Rehabilitation Medicine Training Project of Chinese Medical Association, Foot and Ankle Basics and Orthopedics Group, Orthopedic Branch of Chinese Medical Doctor Association, and Sports Medicine Branch of Jiangsu Medical Association organized relevant experts to formulate Expert consensus on non-surgical treatment for acute lateral ankle sprain ( version 2025), following the principles of scientific vigor, practicality, and innovation. Thirteen recommendations were proposed for standardized treatment protocols across different healing phases, aiming to provide references for standard management of ALAS and improve the therapeutic outcomes.

Acute symptomatic osteoporotic thoracolumbar compression fracture (ASOTLF) can lead to chronic low back pain, kyphosis deformity, pulmonary dysfunction, loss of mobility, and even life-threatening complications. Vertebral augmentation is currently the mainstream treatment method for this condition. In 2019, the Editorial Board of Chinese Journal of Trauma and the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association collaboratively led the development of Clinical guideline for vertebral augmentation for acute symptomatic osteoporotic thoracolumbar compression fractures. Six years later, with advances in clinical diagnosis and treatment techniques as well as accumulating evidence in related fields, the 2019 guideline requires updating. To this end, the Spinal Trauma Group of Orthopedic Surgeons Branch of Chinese Medical Doctor Association, the Spinal Health Professional Committee of China Human Health Science and Technology Promotion Association, and the Minimally Invasive Orthopedics Professional Committee of Shaanxi Medical Doctor Association have organized experts in the field to develop the Clinical guideline for vertebral augmentation of acute symptomatic osteoporotic thoracolumbar compression fractures ( version 2025) , based on the latest evidence-based medical researches. This guideline incorporates 3 recommendations retained from the 2019 version with updated strength of evidence, along with 12 new recommendations. It provides recommendations from six aspects of diagnosis, pain management, treatment option selection, prevention of postoperative complications, anti-osteoporosis therapy, and postoperative rehabilitation, aiming to provide a reference for standard treatment of vertebral augmentation for ASOTLF in hospitals at all levels.

Objective:To relate the changes in electroencephalography (EEG) signals after a spinal cord injury (SCI) with functional independence.Methods:The EEG data describing ninety SCI patients in both open and closed eye states were compared with those collected from 45 healthy counterparts. The SCI patients′ EEG data were correlated with their spinal cord independence measure (SCIM) scores at corresponding time points. The SCI patients were divided into a cervical SCI group (SCI-C group) and a non-cervical SCI group (SCI-NC group), with 45 cases in each group. The difference in EEG data between them and its correlation with the SCIM scores were also compared and analyzed.Results:In the eyes-open state, the EEG power in the frontal, central, temporal, and right occipital regions of the SCI group was lower than among the control group, on average. There were significant differences in the δ and θ low-frequency bands. The α1 band power in the frontal and right parietal regions was significantly higher in the SCI group, on average. With the eyes closed the δ band power in the right prefrontal, frontal, left central, and temporal regions of the SCI group was lower than among the control group, while the α1 band power in the right prefrontal, frontal, central, and parietal regions was significantly higher. The reactivity to eye opening of the α1 band in the right prefrontal, frontal, central, parietal, and temporal regions was less in the SCI patients compared to healthy subjects. Among the SCI patients, higher EEG power in the β2 band of the right frontal lobe and the α2 and β bands of the right temporal lobe was significantly positively correlated with higher SCIM scores during the eyes-open measurements. And the higher EEG power in the α2 band of the prefrontal and frontal lobes, the β2 band of the frontal lobe, the α2 band of the right central region, the α2 and β bands of the temporal lobe, and the α2 and β2 bands of the occipital lobe was significantly positively correlated with higher SCIM scores during the eyes-closed state. The subgroup analysis showed that the δ band power in the left temporal lobe and the α2 band power in the parietal lobe were lower among the SCI-C compared with the SCI-NC patients in the eyes-open state. With the eyes closed, the δ band power in the left frontal, left parietal, and left temporal lobes and the α2 band power in the frontal, central, parietal, temporal, and right occipital lobes was significantly lower in the SCI-C group compared to the SCI-NC group, on average. The reactivity to eye opening of the δ band in the temporal lobe, the α2 band in the left prefrontal, frontal, central, parietal, temporal, and right occipital lobes, and the β2 band in the right parietal and left occipital lobes was less in the SCI-C group than in the SCI-NC group ( P≤0.05). Among the SCI-C patients, higher EEG power in the β1 and β2 bands of the right temporal lobe with the eyes open was significantly positively correlated with higher SCIM scores. With the eyes closed, higher EEG power in the α2 and β1 bands of the right prefrontal lobe was significantly positively correlated with higher SCIM scores. Among the SCI-NC patients, higher EEG power in the δ band of the prefrontal lobe, the β1 and β2 bands of the left prefrontal lobe, and the δ bands of the frontal, central, right parietal, and right temporal lobes during the eyes open measurements was significantly positively correlated with higher SCIM scores. Conclusions:The EEG power of cervical and non-cervical SCI patients shows characteristic changes which correlate with their functional independence.